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Background: Exaggerated exercise blood pressure (EEBP) during clinical exercise testing is associated with poor blood pressure (BP) control and cardiovascular disease (CVD). Type-2 diabetes (T2DM) is thought to be associated with increased prevalence of EEBP, but this has never been definitively determined and was the aim of this study. Methods: Clinical exercise test records were analyzed from 13 268 people (aged 53±13 years, 59% male) who completed the Bruce treadmill protocol (stages 1–4, and peak) at 4 Australian public hospitals. Records (including BP) were linked to administrative health datasets (hospital and emergency admissions) to define clinical characteristics and classify T2DM (n=1199) versus no T2DM (n=12 069). EEBP was defined as systolic BP ≥90th percentile at each test stage. Exercise BP was regressed on T2DM history and adjusted for CVD and risk factors. Results: Prevalence of EEBP (age, sex, preexercise BP, hypertension history, CVD history and aerobic capacity adjusted) was 12% to 51% greater in T2DM versus no T2DM (prevalence ratio [95% CI], stage 1, 1.12 [1.02–1.24]; stage 2, 1.51 [1.41–1.61]; stage 3, 1.25 [1.10–1.42]; peak, 1.18 [1.09–1.29]). At stages 1 to 3, 8.6% to 15.8% (4.8%–9.7% T2DM versus 3.5% to 6.1% no-T2DM) of people with ‘normal’ preexercise BP ( Conclusions: People with T2DM have higher prevalence of EEBP and exercise systolic BP independent of CVD and many of its known risk factors. Clinicians supervising exercise testing should be alerted to increased likelihood of EEBP and thus poor BP control warranting follow-up care in people with T2DM.

AIMS: Cognitive impairment (CI) is highly prevalent in heart failure (HF), and increases patients' risks of readmission. This study sought to determine whether the presence and degree of CI could identify patients most likely to benefit from a HF disease management programme (DMP) to reduce readmissions. METHODS AND RESULTS: A total of 1152 consecutive Australian patients admitted with HF (2014-2017) were prospectively followed up for 12 months. Of these, 324 patients who received DMP (1-month duration, including post-discharge home visits, medication reconciliation, exercise guidance and early clinical review) were matched (1:2 ratio) with 648 usual care patients. Cognitive function was assessed either on the day of or one day before discharge using the Montreal Cognitive Assessment (MoCA). Outcomes included readmission or death at 1, 3 and 12 months, and days at home within 12 months of discharge. Poorer cognitive function was associated with all adverse outcomes. Compared with usual care, DMP was associated with lower odds of 30-day [odds ratio (OR) 0.60, 95% confidence interval 0.40, 0.91] and 90-day (OR 0.53, 95% confidence interval 0.36, 0.77) readmission or death, and with 19 more days at home within 12 months, independent of HF therapy. The effect sizes of these associations were greater for patients with diminished cognition than those with normal cognition (interaction P = 0.036), and might have been more pronounced among those with mild CI compared with those with more severe CI (MoCA score 17-22; OR 0.42, 95% confidence interval 0.21, 0.87) at 30 days (OR 0.31, 95% confidence interval 0.16, 0.60 at 90 days). Patients with normal cognition had fewer events, irrespective of DMP. CONCLUSIONS: Cognitive function may determine how HF patients respond to a DMP. Cognitive screening before implementation of a DMP may allow personalized plans for patients with different levels of cognitive function.

Background Paroxysmal atrial fibrillation (PAF) is associated with cardioembolic risk, however events may occur during sinus rhythm (SR). 4D-flow cardiac magnetic resonance (CMR) imaging allows visualisation of left atrial blood flow, to determine the residence time distribution (RTD), an assessment of atrial transit time. Objective To determine if atrial transit time is prolonged in PAF patients during SR, consistent with underlying atrial stasis. Method 91 participants with PAF and 18 healthy volunteers underwent 4D flow analysis in SR. Velocity fields were produced RTDs, calculated by seeding virtual ‘particles’ at the right upper pulmonary vein and counting them exiting the mitral valve. An exponential decay curve quantified residence time of particles in the left atrium, and atrial stasis was expressed as the derived constant (RTDTC) based on heartbeats. The RTDTC was evaluated within the PAF group, and compared to healthy volunteers. Results Patients with PAF (n = 91) had higher RTDTC compared with gender-matched controls (n = 18) consistent with greater atrial stasis (1.68 ± 0.46 beats vs 1.51 ± 0.20 beats; p = .005). PAF patients with greater thromboembolic risk had greater atrial stasis (median RTDTC of 1.72 beats in CHA₂DS₂-VASc≥2 vs 1.52 beats in CHA₂DS₂-VASc Conclusions Atrial stasis quantified by 4D flow is greater in PAF, correlating with higher CHA₂DS₂-VASc scores. Female gender and systolic dysfunction are associated with atrial stasis. RTD offers an insight into atrial flow that may be developed to provide a personalised assessment of thromboembolic risk.

Obesity and cardiac failure are globally endemic and increasingly intersecting. Bariatric surgery may improve cardiac function and act as a bridge-to-transplantation. We aim to identify effects of bariatric surgery on severe heart failure patients and ascertain its role regarding cardiac transplantation. A retrospective study of a prospectively collected database identified heart failure patients who underwent bariatric surgery between 1 January 2008 and 31 December 2017. Patients were followed up 12 months post-operatively. Cardiac investigations, functional capacity, cardiac transplant candidacy, morbidity and length of stay were recorded. Twenty-one patients (15 males, 6 females), mean age 48.7 ± 10, BMI 46.2 kg/m2 (37.7–85.3) underwent surgery (gastric band (18), sleeve gastrectomy (2), biliopancreatic diversion (1)). There were no loss to follow-up. There was significant weight loss of 26.0 kg (5.0–78.5, p

To describe the use of levosimendan in a quaternary referral center with a dedicated heart failure service and compare its efficacy and safety to continuous outpatient support with inotropes (COSI) among patients with advanced heart failure (AHF) who require bridge-to-decision (BTD) or bridge-to-transplant (BTT) therapy. This study was a retrospective, single-center, descriptive study of patients with AHF who received either a single levosimendan infusion or COSI between 2018 and 2021. A total of 23 patients received a levosimendan infusion, and 14 were started on COSI. Three indications for levosimendan were identified: (1) to facilitate weaning of continuous inotropes, (2) to augment diuresis in cardiorenal syndrome, and (3) as first-line therapy for cardiogenic shock in selected patients. Eighty-three percent (19 of 23) of patients who received levosimendan survived to discharge, and there were few clinically significant adverse events. Overall survival at 12 months among patients who received levosimendan was 74%. No statistically significant difference in survival was observed at 12 months (P = 0.68) or beyond (P = 0.63) between patients who received levosimendan and were discharged with a plan for BTD or BTT and those who received COSI. Levosimendan is a safe and effective short-term therapy in AHF and offers comparable long-term survival to COSI in patients who require BTD or BTT therapy.

Background Cognitive impairment (CI) is highly prevalent in heart failure (HF), and increases patients' risks of readmission. Purpose This study sought to determine whether the presence and degree of CI could identify patients most likely to benefit from a HF disease management program (DMP) to reduce readmissions. Methods 1152 consecutive Australian patients admitted with HF (2014–17) were prospectively followed-up for 12 months. Of these, 324 patients who received DMP (1-month duration, including post-discharge home visits, medication reconciliation, exercise guidance and early clinical review) were matched (1:2 ratio) with 648 usual care patients. Cognitive function was assessed either on the day of or one day before discharge using the Montreal Cognitive Assessment (MoCA). Outcomes included readmission or death at 1-, 3- and 12-months, and days-at-home within 12 months, from discharge. Results Poorer cognitive function was associated with all adverse outcomes. Compared with usual care, DMP was associated with lower odds of 30-day (OR=0.60 [0.40, 0.91]) and 90-day (OR=0.53 [0.36, 0.77]) readmission or death, and with 19 more days-at-home within 12 months, independent of HF therapy. The effect sizes of these associations were greater for patients with diminished cognition than those with normal cognition (interaction p=0.036), and might have been more pronounced among those with mild CI compared with those with more severe CI (MoCA score 17–22, OR=0.42 [0.21, 0.87] at 30-day, OR=0.31 [0.16, 0.60] at 90-day). Patients with normal cognition had fewer events, irrespective of DMP. Conclusions Cognitive function may determine how HF patients respond to a DMP. Cognitive screening before implementation of a DMP may allow personalized plans for patients with different levels of cognitive function Funding Acknowledgement Type of funding sources: None.

Background Home inotropes are utilised in those with end-stage heart failure as a bridge to cardiac transplantation. The use of intravenous dobutamine has been linked to cases of eosinophilic myocardial hypersensitivity (EMH), however, little is known about incidence and predictors. Purpose We sought to examine the incidence and possible predictors of eosinophilic myocardial hypersensitivity in a cohort of patients on home inotrope therapy at a cardiac transplant centre. Methods Patients enrolled in the home inotrope program with progression to heart transplantation or ventricular assist device (VAD) with available myocardial tissue for histopathology, from January 2000 to May 2020 were included. EMH was defined by a pathologist reporting eosinophilic infiltrate with hypersensitivity on myocardial histopathology. Results From a cohort of 74 patients, 58% (43) were on dobutamine and 42% (31) were on milrinone. There were zero cases of EMH in those on milrinone. EMH was identified in 14% (6/43) of patients receiving dobutamine. In the dobutamine cohort, the mean age was 52-±12 years, with 22% being female. Non-ischaemic dilated cardiomyopathy encompassed 62%, the remaining 38% were ischaemic cardiomyopathy. Median dobutamine dose (250 [200–282] mcg/min vs. 225 [200–291] mcg/min) and duration of therapy (41 [23–79] days vs. 53 [24–91] days) were similar between those with and without EMH. Rates of known allergy (27% vs. 33%) and asthma (1 patient in each group) were also similar between those with and without EMH. Those with EMH had a median peak eosinophil count of 0.40×109/L (IQR 0.21–0.66×109/L) compared to a peak of only 0.10×109/L (IQR 0.06–0.29×109/L) in the non-EMH cohort. There was a significant difference in the change in absolute eosinophil count between groups; over the duration of dobutamine therapy the median change in eosinophil count was 0.31×109/L (IQR 0.21–0.59×109/L) in the EMH group compared to 0.03×109/L (IQR 0.00–0.14×109/L) in the non-EMH cohort (p=0.02). Peak C-reactive protein was similar between groups (42±46mg/L vs. 44±45mg/L). Mean left ventricular ejection fraction (LVEF) reduced from 19% (±7%) to 17% (±2%) in those with EMH, while LVEF increased from 20% (±7%) to 22% (±9%) in non-EMH patients (Figure 1), p=NS. Re-presentation with heart failure requiring hospitalisation occurred in 83% in the EMH group compared to only 59% in the non-EMH group (p=0.26). The majority of patients with EMH (83%) required VAD as bridge to transplant, compared to only 41% of non-EMH (p=0.05). Conclusion(s) EMH occurred in 14% of patients receiving home dobutamine. Patients who developed EMH were more likely to require escalation in treatment to VAD as a bridge to heart transplant. In patients receiving dobutamine a reduction in LVEF, hospitalisation with decompensated heart failure and rising eosinophil count should prompt physicians to consider EMH. Funding Acknowledgement Type of funding sources: None. Figure 1

Aims This study aims to determine if traditional markers of disadvantage [female sex, low socio‐economic status (SES), and remoteness] are associated with lower prescription of evidence‐based therapy and higher mortality among patients with moderate–severe heart failure with reduced ejection fraction. Methods and results We recruited 452 consecutive class II–III heart failure with reduced ejection fraction patients. Baseline clinical data were recorded prospectively. The primary outcome was the association of female sex on overall survival. Secondary outcomes included association between evidence‐based therapy delivery and sex and association of SES and remoteness on heart failure therapy and survival. The Australian Bureau of Statistics generated all indices. Median follow‐up was 37.9 months. One hundred and nine patients (24.3%) were women. There was no difference in overall survival based on sex (hazard ratio = 1.19, 95% confidence interval: 0.74–1.92, 0.48). There was no difference in prescription of beta‐blockers [χ 2(1) = 0.91, 0.66], angiotensin‐converting enzyme inhibitors [χ 2(1) = 0.001, 0.97], nor aldosterone antagonists [χ 2(1) = 2.71, 0.10]. There was no difference in rates of primary prevention implantable cardioverter‐defibrillator implantation in men compared with women [χ 2(1) = 0.35, 0.56]. Neither higher SES nor inner city residence conferred an overall survival benefit. Conclusions In this Australian cohort of heart failure patients, delivery of care and likelihood of death are comparable between the sexes, SES groups, and rural vs. city residents.

Background Late gadolinium enhancement (LGE) with cardiac magnetic resonance (CMR) is commonly assumed to represent myocardial fibrosis; however, comparative human histological data are limited, and there is no consensus on the most accurate method for LGE quantitation. We evaluated the relationship between CMR assessment of regional fibrosis and infarct size assessment using serial biomarkers after ST elevation acute myocardial infarction (STEMI). Methods Ninety-three patients treated for STEMI (59 ± 10 years, 86% male) underwent CMR 6 months after infarction. Infarct size was quantified by CMR-LGE using manual and range of semi-automated thresholds (range: 2–10 standard deviations [SD]) above reference myocardium and the full width-half maximum (FWHM) technique, and compared with the rise in serum biomarkers. The agreement between CMR and biomarker in the identification of large infarcts based on peak troponin (TnI) levels was also analysed. Results Quantification methods had a strong influence on the infarct size assessment with CMR-LGE. Significant correlations were observed between LGE and biomarkers across all of the signal intensity thresholds. Whilst there was a wide variation with respect to the estimation of total LGE size (from 6.8 ± 7.7 to 32.1 ± 11.3 grams), the variation in the correlation with peak troponin level was much smaller (r-values ranging from 0.670 to 0.876). There was good agreement between CMR-LGE and biomarker assessment of infarct size; the best agreement between CMR-LGE and large infarction using a threshold of 8SD for peak TnI > 50 ng/mL (Cohen’s kappa (κ) = 0.722), and a threshold of 4SD for peak TnI > 95 ng/mL (κ = 0.761). Conclusions The correlation between CMR-LGE quantification of infarct size and biomarker release following STEMI at a range of semi-automated thresholds was consistently strong, with good agreement between measures across a range of thresholds.

Aims:To estimate the size of regression to the mean with ambulatory blood pressure (ABP) measurement.Methods:Participants from five studies who had repeated blood pressure (BP) measurements using office and ambulatory devices were included. Regression to the mean was calculated following participant

Objectives A hypertensive response to submaximal exercise is associated with cardiovascular disease but this relationship is influenced by functional capacity. Spironolactone improves functional capacity, which could mask treatment effects on exercise blood pressure. This study sought to examine this hypothesis. Design Retrospective analysis of a randomized clinical trial. Methods 102 participants (54 ± 9 years; 52% male) with a hypertensive response to maximal exercise (systolic BP ≥210 mm Hg men; ≥190 mm Hg women) were randomized to 3-month spironolactone 25 mg daily (n = 53) or placebo (n = 49). Submaximal exercise blood pressure was measured during low-intensity cycling (50, 60 or 70% age-predicted maximal heart rate). Functional capacity was measured as maximal oxygen capacity obtained during a maximal treadmill exercise test, and (resting) aortic stiffness by carotid-to-femoral pulse wave velocity. Results Spironolactone improved submaximal exercise systolic blood pressure vs. placebo (−4 ± 16 vs. 2 ± 15 mm Hg, p = 0.045, Cohen's d = 0.42), and had a small (but non-statistically significant) improvement in functional capacity (0.64 ± 5.10 vs. −1.43 ± 5.04 ml/kg/min, p = 0.06, Cohen's d = 0.4). When treatment effects were expressed as the change in submaximal exercise systolic blood pressure relative to the change in functional capacity, a larger effect size was observed (−0.3 ± 1.1 vs. 0.3 ± 1.1 mm Hg/ml·kg·min−1, p = 0.01, Cohen's d = 0.58), but was not explained by improved aortic stiffness. Conclusions Spironolactone reduces submaximal exercise blood pressure, but this treatment effect may be hidden by improved functional capacity and a non-fixed workload. This highlights the most clinically relevant exercise blood pressure is at a low intensity and fixed workload where the influence of fitness on exercise blood pressure is removed, and the effects of therapy can be appreciated.

BACKGROUND Right ventricular (RV) failure after left ventricular assist device (VAD) implantation is a difficult problem. One solution is the implantation of continuous-flow VADs in a biventricular configuration. Disappointing survival and a concerning incidence of right-sided pump thrombosis have been previously reported. METHODS From May 2017 to April 2020, a total of 12 patients underwent implantation of HeartMate 3 (HM3) biventricular VADs (BiVADs) as a bridge to cardiac transplantation. The right-sided pump was implanted in the right atrium in all cases. Adverse events and patient outcomes were determined. RESULTS Patients were male, and the mean age was 44 years. The etiology was dilated cardiomyopathy (6 patients), sarcoid heart disease (2 patients), ischemic cardiomyopathy (1 patient), anthracycline cardiomyopathy (1 patient), non-compaction cardiomyopathy (1 patient), and arrhythmogenic RV cardiomyopathy with biventricular involvement (1 patient). There was 1 death from multisystem failure. There were 3 episodes of right VAD thrombus (thrombosis or clot ingestion); 1 managed medically, 1 recognized intraoperatively treated with clot retrieval, and 1 requiring pump exchange. There were 3 driveline infections. At 18 months after the procedure, 5 patients (41.7%) had undergone cardiac transplantation, 5 patients (41.7%) were alive and on biventricular support, 1 patient had died (8.3%), and 1 patient had VAD explantation for myocardial recovery (8.3%). Actuarial survival at 18 months was 91.7%. CONCLUSIONS In this small study, HM3 BiVAD in these critically ill patients was used with low mortality. This suggests that the timely deployment of biventricular support with HM3 can be associated with favorable outcomes.

Paroxysmal atrial fibrillation (PAF) is associated with cardioembolic risk, however events may occur during sinus rhythm (SR). 4D-flow cardiac magnetic resonance (CMR) imaging allows visualisation of left atrial blood flow, to determine the residence time distribution (RTD), an assessment of atrial transit time.To determine if atrial transit time is prolonged in PAF patients during SR, consistent with underlying atrial stasis.91 participants with PAF and 18 healthy volunteers underwent 4D flow analysis in SR. Velocity fields were produced RTDs, calculated by seeding virtual 'particles' at the right upper pulmonary vein and counting them exiting the mitral valve. An exponential decay curve quantified residence time of particles in the left atrium, and atrial stasis was expressed as the derived constant (RTDPatients with PAF (n = 91) had higher RTDAtrial stasis quantified by 4D flow is greater in PAF, correlating with higher CHA₂DS₂-VASc scores. Female gender and systolic dysfunction are associated with atrial stasis. RTD offers an insight into atrial flow that may be developed to provide a personalised assessment of thromboembolic risk.

Background: A hypertensive response to submaximal exercise is associated with cardiovascular disease but may be influenced by functional capacity. Spironolactone may improve functional capacity, which could mask treatment effects on exercise blood pressure (BP). This study sought to examine this hypothesis. Methods: This was a retrospective analysis of clinical trial data in 102 participants (54 ± 9 years; 52% male) with a hypertensive BP response to peak exercise (systolic BP ≥210 mmHg in men; ≥190 mmHg in women) who were randomised to 3-months spironolactone 25 mg daily (n = 53) or placebo control (n = 49). Submaximal exercise BP was measured during fixed low-intensity cycling (50–70% maximal age-predicted heart rate). Functional capacity was measured as maximal oxygen capacity obtained during a separate maximal treadmill exercise test. Results: Spironolactone improved submaximal exercise systolic BP with a small effect size compared to placebo (−4 ± 16 vs 2 ± 15 mmHg, p = 0.08, Cohen’s d = 0.35), but also functional capacity with a small effect size (0.64 ± 5.10 vs −1.43 ± 5.04 ml/kg/min, p = 0.06, Cohen’s d = 0.41). However, when the change in submaximal exercise systolic BP was expressed relative to the change in functional capacity, there was a significant decrease with spironolactone compared to placebo (−0.3 ± 1.1 vs 0.3 ± 1.1 mmHg/ml.kg.min−1, p = 0.01, Cohen’s d = 0.54). Conclusion: Spironolactone may reduce submaximal exercise BP, but its full treatment effects may be hidden by increased functional capacity. A change in exercise BP should be interpreted according to any change in functional capacity.

Cardiac involvement can occur following bacteremia secondary to Neisseria meningitidis (Garcia et al. Rev Soc Bras Med Trop. 1999;32(5):517–5122) and is likely underrecognized. However, meningococcal disease presenting as primary myopericarditis in immunocompetent adults is a relatively rare phenomenon. We discuss an unusual presentation of meningococcal disease and the investigation and treatment strategies implemented.

Aims In patients with non-ischaemic cardiomyopathy (NICM), the mortality benefit of a primary prevention implantable cardioverter-defibrillator (ICD) has been challenged. Left ventricular (LV) scar identified by cardiac magnetic resonance (CMR) imaging is associated with a high risk of malignant arrhythmia in NICM. We aimed to determine the impact of LV scar on the mortality benefit from a primary prevention ICD in NICM. Methods and results We recruited 452 consecutive heart failure patients [New York Heart Association (NYHA) Class II/III] with NICM and LV ejection fraction ≤35% from a state-wide CMR service. All patients fulfilled European Society of Cardiology guidelines for primary prevention ICD implantation; however, the decision to implant was at the treating physician's discretion. Baseline clinical and CMR data were recorded prospectively and heart failure mortality risk (MAGGIC score) was calculated. The primary study outcome measurement was all-cause mortality based on presence or absence of ICD, stratified by LV scar. Median follow-up was 37.9 months and there was no difference in MAGGIC score between those who did and did not receive a primary prevention ICD (19.30 ± 5.46 vs. 18.90 ± 5.67, P = 0.50). In patients without LV scar, ICD implantation was not associated with improved mortality [hazard ratio (HR) = 1.22, 95% confidence interval (CI): 0.53-2.78, P = 0.64]. In patients with LV scar, ICD implantation was independently associated with reduced mortality (HR = 0.45, 95% CI: 0.26-0.77, P = 0.003). Conclusions In patients with NICM, primary prevention ICD implantation is only associated with reduced mortality in patients with LV scar. This may enable more effective selection of NICM patients for ICD implantation compared with current guidelines.

OBJECTIVES: To investigate whether enrolment of patients in management programs after hospitalisation for heart failure (HF) reduces the likelihood of post-hospital adverse outcomes. DESIGN: Cohort study in which associations between adverse outcomes at 30 and 90 days for people hospitalised for HF and baseline clinical, socio-demographic and blood pathology factors, and with post-discharge management strategies, were assessed. Setting, participants: 906 patients with HF were prospectively enrolled in five Australian states at cardiology departments with expertise in treating people with HF. MAIN OUTCOME MEASURES: All-cause re-admissions and deaths at 30 and 90 days after discharge from the index admission. RESULTS: 58% of patients were men; the mean age was 72.5 years (SD, 13.9 years). By hospital, 30-day re-admission rates ranged from 17% to 33%, and 90-day rates from 40% to 55%; 30-day mortality rates were 0-13%, 90-day rates 4-24%. Factors associated with increased odds of re-admission or death at 30 or 90 days included living alone, cognitive impairment, depression, NYHA classification, left atrial volume index, and Charlson index score. Nurse-led disease management programs and reviews within 7 days were associated with reduced odds of re-admission (but not of death) at 30 and 90 days; exercise programs were associated with reduced odds at 90 days. Significant between-hospital differences in re-admission rates were reduced after adjustment for post-discharge management programs, and abolished by further adjustment for echocardiography findings. Between-hospital differences in mortality were largely explained by differences in echocardiographic findings. CONCLUSIONS: Differences in early re-admission rates after hospitalisation for HF are primarily explained by differences in post-discharge management.

Cardiac Magnetic Resonance derived T1 mapping parameters are a non-invasive method of estimating diffuse myocardial fibrosis. This study aims to to determine the native T1 time, post contrast T1 time and extracellular volume (ECV) derived from T1 mapping and to evaluate the ability of T1 mapping techniques to discriminate healthy myocardium from dilated cardiomyopathy. Seventy-nine participants underwent cardiac magnetic resonance imaging at the Baker Heart and Diabetes Institute, Melbourne, Australia. Fifty-seven healthy volunteers and twenty-two patients with Dilated cardiomyopathy were included in the study. Each participant had T1 mapping sequences performed at 3 T in the mid short axis slice—both SASHA and ShMOLLI T1 mapping were performed. Native T1, post contrast T1 and ECV values were compared in health and dilated cardiomyopathy. Native T1, post contrast T1 and ECV differed significantly between SASHA and ShMOLLI techniques (P

Introduction . The aim of this study was to evaluate the incidence and severity of blunt cardiac injury (BCI) as determined by cardiac magnetic resonance imaging (CMR), and to compare this to currently used diagnostic methods in severely injured patients. Materials and methods . We conducted a prospective, pilot cohort study of 42 major trauma patients from July 2013 to Jan 2015. The cohort underwent CMR within 7 days, enrolling 21 patients with evidence of chest injury and an elevated Troponin I compared to 21 patients without chest injury who acted as controls. Major adverse cardiac events (MACE) including ventricular arrhythmia, unexplained hypotension requiring inotropes, or a requirement for cardiac surgery were recorded. Results . 6/21 (28%) patients with chest injuries had abnormal CMR scans, while all 21 control patients had normal scans. CMR abnormalities included myocardial oedema, regional wall motion abnormalities, and myocardial haemorrhage. The left ventricle was the commonest site of injury (5/6), followed by the right ventricle (2/6) and tricuspid valve (1/6). MACE occurred in 5 patients. Sensitivity and specificity values for CMR at predicting MACE were 60% (15–95) and 81% (54–96), which compared favourably with other tests. Conclusion . In this pilot trial, CMR was found to give detailed anatomic information of myocardial injury in patients with suspected BCI, and may have a role in the diagnosis and management of patients with suspected BCI.

Background: Renal dysfunction is a common complication following heart transplantation that may be worsened by the early initiation of calcineurin inhibitors. Antithymocyte globulin (ATG) or basiliximab has been used to delay or avoid calcineurin inhibitors. The most effective strategy for preventing early acute cellular rejection in this context is uncertain. Methods: We retrospectively reviewed all heart transplant cases between January 2012 and June 2017. The standard therapy consisted of mycophenolate mofetil, prednisolone, and tacrolimus. In patients at high risk of post-transplant renal dysfunction, an early calcineurin inhibitor-free regimen with basiliximab and/or ATG was used. Patients were assigned to cohorts based on the initial immunosuppressive strategy. The primary end point was the freedom rate of acute cellular rejection within 4 weeks post-transplant. Results: Of 93 cases, 21 patients received standard therapy, 64 patients received an initial calcineurin inhibitor-free regimen with basiliximab, and 8 patients received ATG and basiliximab. Freedom from acute rejection was greater in the ATG plus basiliximab group (all rejection free), compared to 40 (63%) of 64 patients treated with basiliximab and 10 (48%) of 21 patients treated with standard therapy ( P < .05, log rank test). In patients treated with basiliximab, early administration (Conclusions: The combination of ATG and basiliximab was more effective in preventing acute cellular rejection. In those patients treated with basiliximab, rejection rates were no worse than standard therapy; however, it was only effective when administered within 24 hours.

Background: Cognitive impairment is a prevalent, independent marker of readmission in heart failure (HF), but the screening is time-consuming. This study sought (1) to identify HF patients at low risk of cognitive impairment (obviating screening) and (2) to simplify a predictive model of HF outcomes by only using cognitive domains that are most predictive. Methods and Results: The Montreal Cognitive Assessment was performed in 1152 Australian patients with HF who were followed for 12 months. One-third (376/1152) of the patients were enrolled into an HF disease management plan to reduce early readmission. Postdischarge outcomes in HF included 30- and 90-day readmission or death and days alive and out of hospital within 12 months of discharge. Cognitive impairment—present in 54% of patients—independently predicted HF outcomes. Normal cognition could be predicted with common clinical and sociodemographic factors with good discrimination (C statistic=0.74 [0.69–0.78]). The visuospatial/executive and orientation domains were most predictive of HF postdischarge outcomes. Using either Montreal Cognitive Assessment score or these 2 domains provided similar incremental values ( P =0.0004 and P =0.0008, respectively) in predicting HF outcomes (both C statistic=0.76) and could similarly identify a group of high-risk patients who benefited most from an HF disease management plan. Conclusions: Cognitive function independently predicts HF outcomes and may also contribute to how a patient responds to intervention. The time and resources spent on cognitive assessment for risk-stratification in HF may be minimized by (1) identifying patients with low risk of cognitive impairment and (2) simplifying the screening instrument to include only the domains that are most predictive of postdischarge outcomes in HF.

INTRODUCTION: Non-sustained ventricular tachycardia (NSVT) is a risk factor for sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). We aimed to assess whether diffuse ventricular fibrosis on cardiac magnetic resonance (CMR) imaging could be a surrogate marker for ventricular arrhythmias in patients with HCM. METHODS: A total of 100 patients with HCM (mean age 51 ± 13 years, septal wall thickness 20 ± 5 mm) underwent CMR with a 1.5 T scanner to determine the presence of ventricular late gadolinium enhancement (LGE) for focal fibrosis, and post-contrast T1 mapping for diffuse ventricular fibrosis. The presence of NSVT was determined by Holter monitoring and a subset of high risk patients received an implantable cardioverter-defibrillator (ICD). RESULTS: NSVT was detected in 23 of 100 patients with HCM. Focal ventricular fibrosis (by LGE) was observed in 87%, with no significant difference between patients with (96%) or without NSVT (86%, P = 0.19). However, LGE mass was greater in patients with (16.5 ± 19.1 g) versus without NSVT (7.6 ± 10.2 g, P < 0.01). NSVT was associated with a significant reduction in ventricular T1 relaxation time (422 ± 54 milliseconds) versus patients without NSVT (512 ± 115 milliseconds; P < 0.001). There was significant reduction in ventricular T1 relaxation time in patients with (430 ± 48 milliseconds) versus without aborted SCD (495 ± 113 milliseconds; P = 0.01) over a mean follow-up of 40 ± 10 months. On multivariate analysis post-contrast ventricular T1 relaxation time and septal wall thickness were the only predictors of NSVT. CONCLUSION: Post-contrast T1 relaxation time on CMR is associated with ventricular arrhythmias in patients with HCM. Diffuse ventricular fibrosis may be an important marker of arrhythmic risk in patients with HCM.

Background: Exaggerated blood pressure (BP) during submaximal exercise independently predicts cardiovascular mortality and identifies uncontrolled high BP not detected at rest. However, thresholds for submaximal exercise BP during clinical exercise testing have never been defined from a large representative sample, which was the aim of this study. Methods: Records from 13,949 people referred for a clinical exercise stress test (aged 52 ± 13 years, 61% male) using the Bruce treadmill protocol (stages 1 to 4 plus peak) were extracted from 4 Australian hospitals over the years 2000–2018. Exercise records were linked to administrative health datasets (hospital admissions and emergency presentations) to define clinical characteristics, including cardiovascular disease history. Thresholds denoting exaggerated BP were defined as > 90th centile at each exercise stage. Results: SBP and DBP thresholds across all stages were higher in males vs. females (stage-1: 180/90 vs 175/90 mmHg; stage-2: 196/94 vs 190/90 mmHg; stage-3: 204/97 vs 196/91 mmHg; stage-4: 210/100 vs 196/92 mmHg; peak: 215/100 vs 206/95 mmHg). SBP at all stages increased stepwise from the 1st to 4th age quartile (p < 0.05), whilst DBP remained similar (stage-1: 163/90 to 185/92 mmHg; stage-2: 180/90 to 204/95 mmHg; stage-3: 193/90 to 210/95 mmHg, stage-4: 200/91, to 210/96 mmHg; peak: 201/95 to 217/100 mmHg). Results were similar irrespective of cardiovascular disease history. Conclusions: This is the first study to define submaximal exercise BP thresholds during clinical exercise testing. Thresholds were higher in males compared to females and increased with age. These thresholds may help clinicians to identify people at increased high BP-related risk.

4D flow cardiac magnetic resonance (CMR) imaging allows visualisation of blood flow in the cardiac chambers and great vessels. Post processing of the flow data allows determination of the residence time distribution (RTD), a novel means of assessing ventricular function, potentially providing additional information beyond ejection fraction. We evaluated the RTD measurement of efficiency of left and right ventricular (LV and RV) blood flow. 16 volunteers and 16 patients with systolic dysfunction (LVEF

New imaging techniques have permitted the detection of subclinical LV dysfunction (LVD) in up to half of patients with type 2 diabetes mellitus (DM) with a normal EF. However, the connection between early LVD and prognosis is unclear. This study aimed to define the long-term outcome of LVD associated with type 2 DM.In this prospective cohort study, 230 asymptomatic patients with type 2 DM underwent measurement of global longitudinal 2D strain (GLS) for detection of LVD and were followed for up to 10 years. All subjects had normal EF (≥50%) and no evidence of coronary artery disease at recruitment. Outcome data were obtained through centralised state-wide death and hospital admission registries. The primary endpoint was all-cause mortality and hospitalisation.On study entry, almost half (45%) of the cohort had evidence of LVD as detected by GLS. Over a median follow-up of 7.4±2.6 years (range 0.6-9.7 years), 68 patients (30%) met the primary endpoint (LVD: 37%; normal LV function: 24%). GLS was independently associated with the primary endpoint (HR=1.10; p=0.04), as was systolic blood pressure (HR=1.02; p0.001) and levels of glycosylated haemoglobin (HR=1.28; p=0.011). Patients with LVD had significantly worse outcome than those without (χ(2)=4.73; p=0.030).Subclinical LVD is common in asymptomatic patients with type 2 DM, is readily detectable by GLS imaging and is independently associated with adverse outcome.Australian and New Zealand Clinical Trials Registry (ACTRN12612001178831).

Background Selecting heart failure (HF) patients for intensive management to reduce readmissions requires effective targeting. However, available prediction scores are only modestly effective. We sought to develop a prediction score for 30-day all-cause rehospitalization or death in HF with the use of nonclinical and clinical data. Methods and Results This statewide data linkage included all patients who survived their 1st HF admission (with either reduced or preserved ejection fraction) to a Tasmanian public hospital during 2009–2012. Nonclinical data (n = 1,537; 49.5% men, median age 80 y) included administrative, socioeconomic, and geomapping data. Clinical data before discharge were available from 977 patients. Prediction models were developed and internally and externally validated. Within 30 days of discharge, 390 patients (25.4%) died or were rehospitalized. The nonclinical model (length of hospital stay, age, living alone, discharge during winter, remoteness index, comorbidities, and sex) had fair discrimination (C-statistic 0.66 [95% confidence interval (CI) 0.63–0.69]). Clinical data (blood urea nitrogen, New York Heart Association functional class, albumin, heart rate, respiratory rate, diuretic use, angiotensin-converting enzyme inhibitor use, arrhythmia, and troponin) provided better discrimination (C-statistic 0.72 [95% CI 0.68–0.76]). Combining both data sources best predicted 30-day rehospitalization or death (C-statistic 0.76 [95% CI 0.72–0.80]). Conclusions Clinical data are stronger predictors than nonclinical data, but combining both best predicts 30-day rehospitalization or death among HF patients.

Existing prediction algorithms for the identification of patients with heart failure (HF) at high risk of readmission or death after hospital discharge are only modestly effective. We sought to validate a recently developed predictive model of 30-day readmission or death in HF using an Australia-wide sample of patients. This study used data from 1,046 patients with HF at teaching hospitals in 5 Australian capital cities to validate a predictive model of 30-day readmission or death in HF. Besides standard clinical and administrative data, we collected data on individual sociodemographic and socioeconomic status, mental health (Patient Health Questionnaire [PHQ]-9 and Generalized Anxiety Disorder [GAD]-7 scale score), cognitive function (Montreal Cognitive Assessment [MoCA] score), and 2-dimensional echocardiograms. The original sample used to develop the predictive model and the validation sample had similar proportions of patients with an adverse event within 30 days (30% vs 29%, p = 0.35) and 90 days (52% vs 49%, p = 0.36). Applying the predicted risk score to the validation sample provided very good discriminatory power (C-statistic = 0.77) in the prediction of 30-day readmission or death. This discrimination was greater for predicting 30-day death (C-statistic = 0.85) than for predicting 30-day readmission (C-statistic = 0.73). There was a small difference in the performance of the predictive model among patients with either a left ventricular ejection fraction of

Aims In hypertrophic cardiomyopathy (HCM), attempts to associate genotype with phenotype have largely been unsuccessful. More recently, cardiac magnetic resonance (CMR) imaging has enhanced myocardial fibrosis characterization, while next-generation sequencing (NGS) can identify pathogenic HCM mutations. We used CMR and NGS to explore the link between genotype and fibrotic phenotype in HCM. Methods and results One hundred and thirty-nine patients with HCM and 25 healthy controls underwent CMR to quantify regional myocardial fibrosis with late gadolinium enhancement (LGE) and diffuse myocardial fibrosis with post-contrast T1 mapping. Collagen content of myectomy specimens from nine HCM patients was determined. Fifty-six HCM patients underwent NGS for 65 cardiomyopathy genes, including 36 HCM-associated genes. Post-contrast myocardial T1 time correlated histologically with myocardial collagen content ( r = −0.70, P = 0.03). Compared with controls, HCM patients had more LGE (4.6 ± 6.1 vs. 0%, P < 0.001) and lower post-contrast T1 time (483 ± 83 vs. 545 ± 49 ms, P < 0.001). LGE negatively correlated with left-ventricular (LV) ejection fraction and outflow tract obstruction, whereas lower post-contrast T1 time, suggestive of more diffuse myocardial fibrosis, was associated with LV diastolic impairment and dyspnoea. Patients with identifiable HCM mutations had more LGE (7.9 ± 8.6 vs. 3.1 ± 4.3%, P = 0.03), but higher post-contrast T1 time (498 ± 81 vs. 451 ± 70 ms, P = 0.03) than patients without. Conclusion In HCM, contrast-enhanced CMR with T1 mapping can non-invasively evaluate regional and diffuse patterns of myocardial fibrosis. These patterns of fibrosis occur independently of each other and exhibit distinct clinical associations. HCM patients with recognized genetic mutations have significantly more regional, but less diffuse myocardial fibrosis than those without.

Background— Successful arrhythmia ablation normalizes ejection fraction (EF) in tachycardia-mediated cardiomyopathy, but recurrent heart failure and late sudden death have been reported. The aim of this study was to characterize the left ventricle (LV) of tachycardia-mediated cardiomyopathy patients long after definitive arrhythmia cure. Methods and Results— Thirty-three patients with a history of successfully ablated incessant focal atrial tachycardia 64±36 months prior, and 20 healthy controls were recruited. At ablation, 18 patients had EFP 55% (AT-normal EF). No subjects had EF of 50% to 55%. Subjects underwent echocardiography with speckle tracking and contrast-enhanced cardiac MRI with ventricular T 1 mapping as an index of diffuse fibrosis. Contrast-enhanced cardiac MRI was performed using a clinical 1.5-T scanner and 0.2 mmol/kg gadolinium-diethylene triamine penta-acetic acid for contrast. Subject characteristics were similar across the 3 groups. Compared with AT-normal EF patients and controls, AT-low EF patients had lower EF (60±6 versus 64±4 and 65±4%; P 2 ; P 2 ; P 1 time (442±53 versus 529±61; P Conclusions— Tachycardia-mediated cardiomyopathy patients exhibit differences in LV structure and function including diffuse fibrosis long after arrhythmia cure, indicating that recovery is incomplete.

Patients presenting with a syndrome of chest pain, elevated cardiac enzyme levels with or without electrocardiogram changes are a common diagnostic and management problem in cardiology. Most commonly, this is due to ischaemic myocardial infarction secondary to coronary artery disease. However, when coronary angiography does not demonstrate any obstructive coronary artery lesion, the diagnosis of myocarditis should be considered. Cardiac magnetic resonance imaging is helpful towards making this diagnosis. Here, we describe the first reported Australian cases of recurrent myocarditis presenting with ischaemic chest pain and elevated cardiac enzyme levels. These cases serve as an important reminder to clinicians that myocarditis is an important mimic of ischaemic myocardial infarction.

Spironolactone is thought to improve aortic stiffness via blood pressure (BP) independent (antifibrotic) effects, but the exact mechanism is unknown. We used metabolomics and hemodynamic measures to reveal the underlying actions of spironolactone in people with a hypertensive response to exercise (HRE). Baseline and follow-up serum samples from 115 participants randomized to 3 months spironolactone (25 mg/day) or placebo were analysed using liquid chromatography/mass spectrometry and nuclear magnetic resonance spectroscopy. Hemodynamic measures recorded at baseline and follow-up included aortic pulse wave velocity (stiffness) and 24 h ambulatory BP. Aortic stiffness was significantly reduced by spironolactone compared with placebo (−0.18 ± 0.17 vs 0.30 ± 0.16 m/s; p 0.05 for all). However, the spironolactone metabolite canrenoate was associated with the change in daytime systolic BP (r = −0.355, p = 0.017) and 24 h pulse pressure (r = −0.332, p = 0.026). This remained highly significant on multiple regression and was independent of age, body mass index and sex. Canrenoate appears to be an active metabolite with BP-dependent effects on the attenuation of aortic stiffness in people with HRE. This finding, together with the lack of change in endogenous metabolites, suggests that the antifibrotic effects of spironolactone could be BP-dependent.

We evaluated the ability of transthoracic echocardiography (TTE) to correctly identify abnormal left ventricular (LV) size, function, and mass when compared to cardiac magnetic resonance (CMR). Whilst numerous studies have compared TTE and CMR with respect to correlation between measurements and study reproducibility, few have employed categorical analysis relevant to clinical practice. Two hundred and fifteen consecutive patients who underwent both TTE and CMR were evaluated for the presence of abnormal LV size, systolic function, and mass. Abnormal LV systolic function was further categorized into grades (mild, moderate, and severe). Quantification of LV morphology and function was performed on TTE and CMR according to published guidelines. The level of agreement between TTE and CMR was compared across binary and categorical variables using Cohen’s kappa. Compared to CMR, TTE demonstrated excellent agreement in identification of abnormal versus normal function (κ = 0.87). However, agreement across grades of LV function was less strong (κ = 0.63). Whilst agreement for identification of severe LV dysfunction was good (κ = 0.68), this would still lead to misclassification of severe dysfunction in approximately one in seven cases. Agreement between TTE and CMR was moderate to good for identification of LV dilation (κ = 0.43–0.63), but poor for identification of increased mass (κ = 0.04). Whilst in clinical practice TTE performs well in identification of normal versus abnormal systolic function, it has substantial limitations across grades of dysfunction and in the assessment of LV size and mass. These limitations have important implications when considering management decisions for patients based on thresholds of LV morphology or function.

Cognitive impairment is highly prevalent in heart failure (HF), and may be associated with short-term readmission. This study investigated the role of cognition, incremental to other clinical and non-clinical factors, independent of depression and anxiety, in predicting 30-day readmission or death in HF.This study followed 565 patients from an Australia-wide HF longitudinal study. Cognitive function (MoCA score) together with standard clinical and non-clinical factors, mental health and 2D echocardiograms were collected before hospital discharge. The study outcomes were death and readmission within 30days of discharge. Logistic regression, Harrell's C-statistic, integrated discrimination improvement (IDI) and net reclassification index were used for analysis.Among 565 patients, 255 (45%) had at least mild cognitive impairment (MoCA≤22). Death (n=43, 8%) and readmission (n=122, 21%) within 30days of discharge were more likely to occur among patients with mild cognitive impairment (OR=2.00, p=0.001). MoCA score was also negatively associated with 30-day readmission or death (OR=0.91, p0.001) independent of other risk factors. Adding MoCA score to an existing prediction model of 30-day readmission significantly improved discrimination (C-statistic=0.715 vs. 0.617, IDI estimate 0.077, p0.001). From prediction models developed from our study, adding MoCA score (C-statistic=0.83) provided incremental value to that of standard clinical and non-clinical factors (C-statistic=0.76) and echocardiogram parameters (C-statistic=0.81) in predicting 30-day readmission or death. Reclassification analysis suggests that addition of MoCA score improved classification for a net of 12% of patients with 30-day readmission or death and of 6% of patients without (p=0.002).Mild cognitive impairment predicts short-term outcomes in HF, independent of clinical and non-clinical factors.

Background A hypertensive response to exercise (HRE; defined as normal clinic blood pressure (BP) and exercise systolic BP (SBP) ≥210 mm Hg in men or ≥190 mm Hg in women, or diastolic BP (DBP) ≥105 mm Hg) independently predicts mortality. The mechanisms remain unclear but may be related to masked hypertension. This study aimed to assess the prevalence of masked hypertension and its association with cardiovascular risk factors, including left ventricular (LV) mass, in patients with a HRE. Methods Comprehensive clinical and echocardiographic evaluation (including central BP, aortic pulse wave velocity by tonometry) and 24-h ambulatory BP monitoring (ABPM) were performed in 72 untreated patients with HRE (aged 54 ± 9 years; 60% male; free from coronary artery disease confirmed by exercise stress echocardiography). Masked hypertension was defined according to guidelines as daytime ABPM ≥135/85 mm Hg and clinic BP 0.05 for both). The strongest independent determinant of LV mass index was the presence of masked hypertension (unstandardized β = 5.6; P = 0.007), which was also independently related to LV RWT (unstandardized β = 0.04; P = 0.03). Conclusions Masked hypertension is highly prevalent in HRE patients with a normal resting office BP and is associated with increased LV mass index and RWT. Clinicians should consider measuring ABPM or home BP in HRE patients.

Background— Diastolic dysfunction (DD) is associated with adverse cardiovascular outcomes. We studied the impact of an exercise-based lifestyle intervention on the evolution of DD in patients with type 2 diabetes mellitus (T2DM) and prospectively investigated the clinical correlates of DD progression. Methods and Results— A total of 223 outpatients with T2DM were randomized to supervised exercise-based lifestyle intervention (initial gym-based program and lifestyle and diet advice followed by telephone-guided supervision) or usual care. Patients underwent echocardiographic assessment of diastolic function and metabolic and clinical evaluation at baseline and 3 years. Changes in prevalence and evolution of DD were assessed and correlations sought with clinical and metabolic variables. DD was present in 50% of patients at baseline and 54% at 3 years, with no difference between the usual care and intervention groups (60% versus 48%, P =0.10). Abnormal DD at the final visit was independently associated with older age and a decrease in peak oxygen consumption over time ( P P =0.034), with the only other independent correlate being older age (β=0.05; odds ratio, 1.06; P =0.019). Conclusions— Despite being efficacious in the subgroup who completed 3 years of exercise-based lifestyle intervention, randomization to this program was not effective in reducing progression of subclinical DD in patients with T2DM, which may reflect the recognized difficulty of adherence to prolonged exercise intervention. Clinical Trial Registration— URL: http://www.anzctr.org.au . Unique identifier: ACTRN12607000060448.